Generation and characterisation G-protein-coupled receptor monoclonal antibodies utilising detergent-free solubilisation

近年来，抗体作为治疗剂的开发有显著增长。特别有益的是它们的精致特异性，甚至在共享天然激动剂的保守配体结合位点的密切相关的受体亚型之间。该项目旨在与领先的制药/生物技术公司UCB合作，利用新型抗体生成平台，以提高和纯化针对G蛋白偶联受体（GPCR）的单克隆抗体。GPCR是最大的膜受体家族，具有重要的药理学意义，目前约有30-40%的药物靶向这些受体;对更有效的药物有巨大的需求。到目前为止，我们已经成功地提出了一种A类GPCR的推定抗体，并旨在提出其他类别和不同类型的GPCR的抗体。替代受体表达系统和增溶方法也将在本项目期间进行探索，涉及新型聚合物，利用最新的无去污剂方法。根据抗体的表征结果，也有可能进入活细胞的表征，将免疫组织化学纳入项目。

In recent years, there has been significant growth in the development of antibodies as therapeutic agents. Of particular benefit is their exquisite specificity, even between closely-related receptor subtypes sharing a conserved ligand binding site for the natural agonist. This project aims to utilise a novel antibody generation platform in collaboration with leading pharmaceutical/bio-technology company, UCB, to raise and pharmacologically characterise monoclonal antibodies targeting G-Protein-Coupled receptors (GPCRs). GPCRs are the largest family of membrane receptors and are of great pharmacological significance, with around 30-40% of current drugs targeting these receptors; and a huge demand for more effective medicines. We have successfully raised putative antibodies for one class A GPCR so far, and aim to raise antibodies from other classes and different types of GPCRs. Alternative receptor expression systems and solubilisation methods will also be explored during this project, involving novel polymers, utilising the latest, detergent free methods. Dependent upon characterisation outcomes of the antibodies there is also potential to move into characterisation in live cells, incorporating immunohistochemistry into the project.